The Genotype-Drug Connection

Heredity affects drug effects more than you may realize.

The study of pharmacogenetics is expanding and garnering well-deserved attention.

Although drug-drug interactions have long been recognized as a leading cause of adverse drug reactions, pharmacogeneticists have recently described two new types of interaction:

A drug-gene interaction (DGI) that occurs when a patient's CYP450 genotype (e.g., CYP2D6 poor metabolizer) limits his or her body's ability to process and use a drug.

A drug–drug–gene interaction (DDGI) that occurs when the patient's CYP450 genotype and a drug in a patient's current treatment regimen (e.g., a CYP2D6 inhibitor) affects his or her body's ability to process and use another drug.

These gene-drug interactions occur more frequently than one might expect.

Of the 1,053 potentially clinically significant drug interactions identified by Paul Verbeurgt and colleagues in a recent study, a genotype-drug connection accounted for 33.9% - DGIs accounted for 14.7% of interactions, and DDGIs accounted for 19.2% of interactions.1

Extrapolated across the U.S. population, these and similar findings suggest a new approach to significantly improving medication safety and reducing avoidable adverse events – i.e., devising a convenient, cost-effective method for conveying patient-specific genetic and pharmaceutical information to the clinician at the point of care.

Of course, the devil is in the details, but I am aware of at least one innovative program that is making it possible to include DGIs and DDGIs in personalized prescribing.

A white paper released in August, 2014, described YouScript® Personalized Prescribing software, a medication management system that helps clinicians assess the cumulative effect of a patient's entire drug regimen and genetic profile.

Reports from early adopters illustrate how this new technology might be applied in a variety of real-world clinical settings:

The Stone Run Family Medicine practice in Rising Sun, Md., uses the system for population-wide testing and risk analyses.

Because the effectiveness of many postoperative drug options is dependent on a patient's genetics and medication regimen, Kentucky Orthopedic & Hand Surgeons rely on the system for pre-operative care planning and postoperative pain management.

In addition to improving patient care and patient experience, The University of Kentucky's Gill Heart Institute has begun to use the system to better tailor therapies – and reduce overall costs.

It doesn't take a crystal ball to predict that, as CYP testing becomes the new norm and pharmacogenetic research gains momentum, a growing number of potentially harmful drug-gene interactions will be avoided.

Reference:

1. Verbeurgt P, Mamiya T, Oesterheld J. How common are drug and gene interactions? Prevalence in a sample of 1143 patients with CYP2C9, CYP2C19 and CYP2D6 genotyping. Pharmacogenomics (2014); 15(5):655-665.

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